New drugs are tested to determine their toxicity, pharmacokinetics (PK) and adsorption, distribution, metabolism and excretion (ADME), profiles within animal or model systems. It is preferred that these studies are done in vitro prior to in vivo tests. Multiwell insert devices have an upper chamber, which is separated from a lower chamber by a membrane, and can be used to conduct such studies. See, e.g., US 2004/0091397. The upper chamber and membrane are part of a unit that can be removed from the apparatus forming the lower chamber.
ADME studies can include, e.g., cell migration assays, wherein cells are placed in the upper chamber of a multiwell insert device and allowed to migrate through the membrane into the lower chamber. The cells are detected via staining or fluorescent labels, which can be expensive and time consuming.
Additionally, drug adsorption assays can be performed with multiwell insert devices. Drug adsorption assays determine permeability of drugs across the membrane. Detection of the drug is often accomplished by liquid chromatography followed by mass spectrometry (LC/MS) and by UV visible spectrophotometry. However, these detection methods are cumbersome, have low throughput, can require large amounts of sample, and are end-point assays.
Therefore, methods are needed in the art that do not require labels, is high throughput, and can detect changes in real-time.